Technologically enhanced naturally occurring radioactive materials in the oil industry (TENORM).

A large amount of naturally occurring radioactive materials in the form of by-products or waste is produced annually by the growing activity of the oil and gas industry. Solid scale, sludge and produced water are typical residues contaminated with natural radionuclides from the uranium and thorium series, particularly 226Ra and 228Ra. The observed specific activities of these radionuclides are in the ranges up to 3700 kBq/kg and up to 168 kBq/kg for solid scale and sludge, respectively. The average activities of both radionuclides exceed the exemption level of 10,000 Bq/kg recommended by IAEA safety standards. This means that TENORM wastes from the oil industry may generate radiation exposure levels which require attention and continuous monitoring during some routine operations in this industry. This exposure is mostly caused by external gamma radiation coming from the 226Ra radionuclide and its progenies

Determination of the sediment deposition rates in the Kuwait Bay using 137Cs and 210Pb

Five bottom sediment cores from the Kuwait Bay were dated using 210Pb and 137Cs radionuclides. For evaluating the sedimentation rate two methods were applied: geochronology with the constant rate of supply unsupported 210Pb (CRS model) and the Weibull distribution of anthropogenic 137Cs. The sedimentation rates in this region, calculated by the first method ranged from 0.24 to 0.39 cm/year, while the same rates obtained from 137Cs distribution were slightly lower: from 0.1 to 0.25 cm/year. These relatively small differences can be explained by additional input of the Chernobyl accident to the 137Cs inventory in the bottoms sediments of the Northern Hemisphere

Profiling Cisplatin Resistance in Head and Neck Cancer: A Critical Role of the VRAC Ion Channel for Chemoresistance

Treatment success of head and neck cancers (HNSCC) is often hindered by tumor relapses due to therapy resistances. This study aimed at profiling cisplatin resistance mechanisms and identifying biomarkers potentially suitable as drug targets and for patient stratification. Bioinformatic analyses of suggested resistance factors in a cohort of 565 HNSCC patients identified the VRAC ion channel as a clinically relevant indicator for recurrent diseases following radiochemotherapy (p = 0.042). Other drug import/export transporters, such as CTR1, OCT1, or MRP1, were found to be less relevant. To experimentally verify VRAC’s critical role for cisplatin resistance, we used CRISPR/Cas9 knockout resulting in cisplatin-resistant HNSCC cells, which could be resensitized by VRAC expression. Next-generation sequencing further underlined VRAC’s importance and identified VRAC-regulated signaling networks, potentially also contributing to cisplatin resistance. CTR1, OCT1, or MRP1 did not contribute to increased cisplatin resistance. In addition to two-dimensional HNSCC models, three-dimensional tumor spheroid cultures confirmed VRAC’s unique role for cisplatin sensitivity. Here, resistance correlated with DNA damage and downstream apoptosis. The cisplatin specificity of the identified VRAC pathway was verified by testing paclitaxel and doxorubicin. Our results were independently confirmed in naturally occurring, cisplatin-resistant HNSCC cancer cell models. Collectively, we here demonstrate VRAC’s role for cisplatin resistance in HNSCC and its relevance as a potential drug target and/or prognostic biomarker for chemotherapy resistance

Csy4 relies on an unusual catalytic dyad to position and cleave CRISPR RNA

CRISPR-Cas adaptive immune systems protect prokaryotes against foreign genetic elements. crRNAs derived from CRISPR loci base pair with complementary nucleic acids, leading to their destruction. In Pseudomonas aeruginosa, crRNA biogenesis requires the endoribonuclease Csy4, which binds and cleaves the repetitive sequence of the CRISPR transcript. Biochemical assays and three co-crystal structures of wild-type and mutant Csy4/RNA complexes reveal a substrate positioning and cleavage mechanism in which a histidine deprotonates the ribosyl 2′-hydroxyl pinned in place by a serine, leading to nucleophilic attack on the scissile phosphate. The active site catalytic dyad lacks a general acid to protonate the leaving group and positively charged residues to stabilize the transition state, explaining why the observed catalytic rate constant is ∼10(4)-fold slower than that of RNase A. We show that this RNA cleavage step is essential for assembly of the Csy protein-crRNA complex that facilitates target recognition. Considering that Csy4 recognizes a single cellular substrate and sequesters the cleavage product, evolutionary pressure has likely selected for substrate specificity and high-affinity crRNA interactions at the expense of rapid cleavage kinetics